Summit Therapeutics (Nasdaq: SMMT) is extending its challenge to Merck's Keytruda beyond lung cancer, launching a Phase II/III trial of ivonescimab plus Astellas/Pfizer's Padcev (enfortumab vedotin) against pembrolizumab (Keytruda) plus enfortumab vedotin as first-line treatment for previously untreated locally advanced or metastatic urothelial carcinoma.
HARMONi-GU1 is the first ivonescimab study in a genitourinary malignancy and targets the pembrolizumab-plus-enfortumab vedotin regimen that has become the global standard of care following the EV-302/KEYNOTE-869 trial. Approximately 800 patients will be enrolled, with progression-free survival (PFS) and overall survival (OS) as the Phase III primary endpoints.
The expansion builds on positive Phase III results generated with the Akeso-discovered PD-1/VEGF bispecific antibody in non-small cell lung cancer (NSCLC). Summit licensed ex-China rights to ivonescimab from Akeso in 2022, while the drug is already approved in China for two NSCLC indications. Most recently, the Phase III HARMONi-6 study showed ivonescimab plus chemotherapy reduced the risk of death by 34% versus BeiGene's PD-1 Tevimbra (tislelizumab) plus chemotherapy in squamous NSCLC, marking the first overall survival benefit reported over a PD-1-based regimen in a head-to-head Phase III study. A US FDA decision on Summit's biologics license application in EGFR-mutant NSCLC is expected by November 14, 2026.
Ivonescimab simultaneously targets PD-1 and VEGF, with Summit citing the central role of immune evasion and angiogenesis in urothelial carcinoma as the rationale for expansion. The trial also continues the company's strategy of combining ivonescimab with established antibody-drug conjugates rather than developing entirely new treatment backbones.